We are continuing to evaluate polyamines as biochemical markers of cancer. Polyamine levels have been and are being measured in the plasma and urine of cancer patients before and after multi-modality therapy in an attempt to assess their efficacy as markers of response to therapy. We have found that the level of putrescine in both plasma and urine prescribed quite accurately the number of cells progressing through cell cycle, whereas spermidine concentration in plasma and urine appears to be related to the cell loss factor of the tumor. Current studies are evaluating the optimal times of sampling and the optimal body fluid with preliminary data suggesting that plasma levels are more reliable than serum samples. Expressing the data as polyamines per unit creatinine appears to accurately control for unreliable collection procedures when one is dealing with 24-hr samples. Four-hr urine samples appear to be as reliable as 24-hr samples, and we are in the process of evaluating polyamine levels in spot urine as they relate to longer collection times. We are attempting to develop more rapid assays for polyamines which could be applied to the clinical situation. Rabbits have been injected with polyamines coupled to Sepharose beads in an attempt to raise specific antibodies. Work is in progress to further elucidate the mechanism of induction of ornithine decarboxylase (ODC) in normal and neoplastic growth. The major inductive mechanism appears to involve genetic transcription and is related to de novo synthesis of the enzyme. Therefore, increased rate of synthesis of the enzyme would appear to be the major regulatory pathway at this time. Minor exceptions include serum stimulation which results in a short-term alteration in the half-life of the enzyme, i.e., alteration of degradative rate of the enzyme. Progress is being made toward an understanding of the mechanism by which ODC, the rate-limiting enzyme in polyamine biosynthesis, affects the kinetic parameters of RNA polymerase I. At this time, it appears that ODC may function as an initiation factor for RNA polymerase I. Because of the importance of polyamines in growth, both normal and neoplastic, and because their extracellular levels appear to reflect pathology, current studies are focussed in order to provide the most rapid transfer of knowledge from the basic studies to the clinical application.